摘要
为探索食物砷暴露对肝脏脂质代谢的作用及其分子机制,该研究构建了长时间喂养含砷饲料的C57BL/6小鼠模型及HepG2细胞模型。利用透射电子显微镜观察小鼠肝脏切片的超微结构,通过免疫印迹及试剂盒法检测细胞脂质代谢相关指标。结果显示,砷暴露小鼠肝脏脂滴明显减少、变小。体外实验中,HepG2细胞在10、20、30、40μmol/L砷暴露后,固醇调节元件结合蛋白1c(Sterol Regulatory Element-Binding Protein 1c,SREBP-1c)相对表达分别为0.73、0.60、0.54、0.40,脂肪酸合成酶(Fatty Acid Synthase,FASN)相对表达水平分别为0.88、0.77、0.75、0.82;甘油三酯(Triglyceride,TG)相对表达分别为0.94、0.78、0.78、0.73;胆固醇(Total Cholesterol,TC)相对表达分别为0.95、0.73、0.70、0.57,细胞脂质代谢发生紊乱。细胞外信号调节激酶(Extracellular Signal-Regulated Kinase,ERK)磷酸化相对表达水平分别为5.72、23.78、33.20、47.17,ERK信号通路被激活。ERK抑制剂PD98059预处理后,HepG2细胞的SREBP-1c、FASN相对表达水平分别上升至1.2、1.3;TG、TC相对表达也分别恢复到1.2、1.2。该研究为ERK信号在砷暴露引起HepG2细胞脂质代谢紊乱中的作用提供了理论基础。
To investigate the impact of dietary arsenic exposure on hepatic lipid metabolism and its underlying molecular mechanisms,C57BL/6 mice were chronically fed arsenic-containing chow,and an arsenic-exposed HepG2 cell model was used.Mouse liver structure was examined with transmission electron microscopy,and lipid metabolism indicators in HepG2 cells were analyzed through immunoblotting and assay kits.Results showed a significant reduction in both the number and size of lipid droplets in the livers of the arsenic-exposed group.In vitro experiments revealed decreased expression of Sterol Regulatory Element Binding Protein-1c(SREBP-1c)and Fatty Acid Synthesis(FASN)proteins in HepG2 cells exposed to arsenic concentrations ranging from 10 to 40μmol/L(SREBP-1c:0.73,0.60,0.54,0.40;FASN:0.88,0.77,0.75,0.82).Levels of triglycerides(TG)and total cholesterol(TC)also declined(TG:0.94,0.78,0.78,0.73;TC:0.95,0.73,0.70,0.57),indicating arsenic-induced lipid metabolism disruption.Additionally,phosphorylated Extracellular Signal-Regulated Kinase(ERK)expression increased significantly following arsenic exposure(5.72,23.78,33.20,47.17),suggesting ERK pathway activation.Pre-treatment with PD98059,an ERK activation inhibitor,led to increased SREBP-1c and FASN expression in arsenicexposed HepG2 cells(SREBP-1c:1.2;FASN:1.3),as well as elevated TG and TC levels(TG:1.2;TC:1.2).These findings provide a theoretical basis for the role of ERK signaling in arsenic-induced lipid metabolism disorders in HepG2 cells.
作者
张文鑫
曾淑娴
田先兵
吴杰根
郭莲仙
梁一
ZHANG Wenxin;ZENG Shuxian;TIAN Xianbing;WU Jiegen;GUO Lianxian;LIANG Yi(Department of Clinical Immunology,Institute of Laboratory Medicine,Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,School of Medical Technology,Guangdong Medical University,Dongguan 523808,China;Central Laboratory,Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College),Shenzhen 518172,China;School of Public Health,Guangdong Medical University,Dongguan 523808,China)
出处
《现代食品科技》
北大核心
2025年第1期1-7,共7页
Modern Food Science and Technology
基金
国家自然科学基金项目(81102850)
广东省医学科研基金项目(A2022392)
广东医科大学专业建设项目(4SG21014G)。
关键词
砷
细胞外信号调节激酶
脂质代谢
arsenic
extracellular signal-regulated kinase(ERK)
lipid metabolism
